Why It Matters

Researchers and doctors who inject stem cells into the body currently have limited ways of knowing where such cells go or if they survive.

Giving patients stem cells packaged with silica nanoparticles could help doctors determine the effectiveness of the treatments by revealing where the cells go after they’ve left the injection needle.

Researchers from Stanford University School of Medicine report in a paper published on Wednesday in the journal Science Translational Medicine that silica nanoparticles taken up by stem cells make the cells visible on ultrasound imaging. While other imaging techniques such as MRI can show where stem cells are located in the body, that method is not as fast, affordable, or widely available as an ultrasound scanner, and more importantly, it does not offer a real-time view of injection, say experts.

Stem cells have significant medical promise because they can be turned into other types of living cell. As well as helping doctors adjust therapeutic dosages in patients, the new technique could help scientists perfect stem cell treatments, says senior author Sanjiv Gambhir. “For the most part, researchers shoot blindly—they don’t quite know where the cells are going when they are injected, they don’t know if they home in to the right target tissue, they don’t know if they survive, and they don’t know if they leak into other tissue types,” says Gambhir.

This, in part, could be slowing advances in stem cell treatments. “If stem cells are going to be used as a legitimate medical treatment for the repair of damaged or diseased tissue, then we will need to know precisely where they are going so the treatments can be optimized,” says Lara Bogart, a physicist at the University of Liverpool. Bogart is developing magnetic nanoparticles for tracking stem cells using MRI.

To get a better view of where cells are going during and after injection, Gambhir and colleagues used nanoparticles made of silica, a material that reflects sound waves, so it can be detected in an ultrasound scan. The nanoparticles were incubated with mesenchymal stem cells, which can develop into cell types including bone cells, fat cells, and heart cells. The cells ingested the nanoparticles, which did not change the cells’ growth rate or ability to develop into different cell types. Inside the cells, the nanoparticles clumped together, which made them more visible in an ultrasound.

The researchers then injected the nanoparticle-laden stem cells into the hearts of mice and tracked their movements. Many research groups are testing stem cells as a treatment after a heart attack or for other heart conditions in both lab animals (see “A Step Toward Healing Broken Hearts with Stem Cells” and “Injecting Stem Cells into the Heart Could Stop Chronic Chest Pain”) as well as in patients in clinical trials. A fast and real-time imaging tool could help because researchers and doctors need to be sure that the cells reach the most beneficial spots in a sickly heart.

“It’s very important to know where you inject the cells because you don’t want to put them in areas damaged by the heart attack; that tissue is dead and a very hostile environment,” says Jeff Bulte, a cell engineer at the Johns Hopkins University School of Medicine who was not involved in the study. “On the other hand, you want to place them as close to the site of damage as possible,” he says.

The silica nanoparticles can also be detected in MRI machines because they contain a strongly magnetic heavy metal known as gadolinium that shows up in the scans. And they can be detected optically (through microscopes) because they carry a fluorescent dye. “This gives us three complementary ways to image the same particle,” says Bogart. Depending on the part of the body receiving the transplant, the type of scanner available and the amount of time since injection, a researcher may choose one method over another.

The mice used in the study were healthy, but the team plans to test the tracking method in mice or other lab animals that have heart damage. The team will also use the nanoparticles in different cell types and do more toxicity studies prior to filing for FDA approval to test the nanoparticles in humans. “It will be about a three-year process to do first-in-man studies,” says Gambhir.